Liposome-encapsulated hemoglobin reduces the size of cerebral infarction in the rat - Evaluation with photochemically induced thrombosis of the middle cerebral artery

Liposome-encapsulated hemoglobin reduces the size of cerebral infarction in the rat - Evaluation with photochemically induced thrombosis of the middle cerebral artery
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DOI:
10.1161/strokeaha.106.467290
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发表时间:
2007-05-01
期刊:
影响因子:
8.3
通讯作者:
Tsukada, Hideo
Tsukada, Hideo
中科院分区:
医学1区
文献类型:
--
作者:
Kawaguchi, Akira T.;Fukumoto, Dai;Tsukada, Hideo

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背景和目的-脂质体包裹血红蛋白(莱赫; TRM-645)是一种新型氧(O(2))载体,其O(2)亲和力(P(50)O(2)=40 mm Hg)低于红细胞。与无细胞血红蛋白相反,包裹防止血红蛋白外渗,而其亚细胞大小(230 nm)可改善O(2)的输送并限制脑梗死的严重程度。在光化学诱导大脑中动脉血栓形成后24小时,通过氯化三苯基四氮唑染色检测接受no的大鼠的梗死综合区,处理、10 mL/kg的莱赫、同源血、空脂质体或盐水。为了建立剂量-反应关系,莱赫剂量从10 mL/kg减少到2 mL/kg、0.4 mL/kg和0.08 mL/kg。结果-接受莱赫的大鼠与未接受输注、生理盐水、空脂质体或皮质输血但未接受基底神经节输血的动物相比,梗死程度得到显著抑制。剂量-反应关系显示,低至2 mL/kg的莱赫是保护,而总血O(2)的含量,血红蛋白水平,输血和/或输注空脂质体或salineswere not effective.Conclusions -我们的研究结果表明,莱赫显着减少了面积的梗死后皮层,但不是在基底神经节的大鼠大脑中动脉的光化学诱导血栓形成。
Background and Purpose - Liposome-encapsulated hemoglobin ( LEH; TRM-645) is a novel oxygen ( O(2)) carrier with a lower O(2) affinity ( P(50)O(2)=40 mm Hg) than red blood cells. In contrast to cell-free hemoglobin, encapsulation prevents hemoglobin extravasation, whereas its subcellular size ( 230 nm) may improve O(2) delivery and limit the severity of cerebral infarction.Methods - The extent of cerebral infarction was determined 24 hours after photochemically induced thrombosis of the middle cerebral artery from the integrated area of infarction detected by triphenyltetrazolium chloride staining in rats receiving no treatment, 10 mL/kg of LEH, homologous blood, empty liposomes, or saline. To develop a dose-response relationship, LEH dose was reduced from 10 mL/kg to 2 mL/kg, 0.4 mL/kg, and 0.08 mL/kg.Results - Infarction extent was significantly suppressed in rats receiving LEH as compared with animals receiving no infusion, saline, empty liposome, or transfusion in the cortex but not in the basal ganglia, where all had similar degrees of damage. The dose-response relationship revealed that as little as 2 mL/kg of LEH was protective, whereas the total blood O(2) content, hemoglobin level, and transfusion and/or infusion of empty liposomes or saline were not effective.Conclusions - Our results suggest that LEH significantly reduces the area of infarction in the cortex but not in basal ganglia after photochemically induced thrombosis of the middle cerebral artery in the rat.